Summary

Human and animal studies have demonstrated that the prenatal environment affects adult health and disease. Epidemiological studies have shown that gestational exposure to maternal starvation or overnutrition of the paternal grandfather is linked to increased risks for cardiovascular diseases and diabetes (1, 2). In both cases, adverse metabolic health outcomes can be transmitted multigenerationally. As well, pregnant rats fed low-protein diets produced two sequential generations of offspring that became diabetic as adults (3). Nevertheless, despite considerable research efforts elaborating the phenotypic consequences of in utero insults to adult offspring and to their progeny, the mechanisms mediating multigenerational effects are unclear. On page 1255903 of this issue, Radford et al. (4) undertook an in-depth, genome-wide approach using a mouse model of undernutrition. This model has been linked to low birth weight, glucose intolerance, and reduced pancreatic function in two subsequent generations (5). Radford et al. not only provide convincing mechanistic insights about the transmission of phenotypes to later generations, their findings also suggest a path forward for pursuing these types of detailed studies.